Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Morelos, 62210, Mexico.
J Biol Phys. 2023 Dec;49(4):393-413. doi: 10.1007/s10867-023-09645-z. Epub 2023 Oct 18.
The membrane potential of a cell (V) regulates several physiological processes. The voltage sensor domain (VSD) is a region that confers voltage sensitivity to different types of transmembrane proteins such as the following: voltage-gated ion channels, the voltage-sensing phosphatase (Ci-VSP), and the sperm-specific Na/H exchanger (sNHE). VSDs contain four transmembrane segments (S1-S4) and several positively charged amino acids in S4, which are essential for the voltage sensitivity of the protein. Generally, in response to changes of the V, the positive residues of S4 displace along the plasma membrane without generating ionic currents through this domain. However, some native (e.g., Hv1 channel) and mutants of VSDs produce ionic currents. These gating pore currents are usually observed in VSDs that lack one or more of the conserved positively charged amino acids in S4. The gating pore currents can also be induced by the isolation of a VSD from the rest of the protein domains. In this review, we summarize gating pore currents from all families of proteins with VSDs with classification into three cases: (1) pathological, (2) physiological, and (3) artificial currents. We reinforce the model in which the position of S4 that lacks the positively charged amino acid determines the voltage dependency of the gating pore current of all VSDs independent of protein families.
细胞的膜电位（V）调节着几种生理过程。电压传感器域（VSD）是一个赋予不同类型跨膜蛋白电压敏感性的区域，例如：电压门控离子通道、电压感应磷酸酶（Ci-VSP）和精子特异性 Na/H 交换器（sNHE）。VSD 包含四个跨膜片段（S1-S4）和 S4 中的几个正电荷氨基酸，这些对于蛋白质的电压敏感性至关重要。通常，响应 V 的变化，S4 的正电荷残基在没有通过该结构域产生离子电流的情况下沿质膜移位。然而，一些天然（例如，Hv1 通道）和 VSD 的突变体产生离子电流。这些门控孔电流通常在 S4 中缺少一个或多个保守的正电荷氨基酸的 VSD 中观察到。门控孔电流也可以通过将 VSD 从其余蛋白质结构域中分离出来而诱导。在这篇综述中，我们总结了具有 VSD 的所有蛋白家族的门控孔电流，并将其分为三种情况：（1）病理性，（2）生理性和（3）人工电流。我们加强了这样的模型，即缺乏正电荷氨基酸的 S4 的位置决定了所有 VSD 的门控孔电流的电压依赖性，而与蛋白家族无关。
